Targeting Immune Cell Metabolism: A Promising Therapeutic Approach for Cardiovascular Disease DOI Open Access

Dexiang Xia,

Qinwen Zheng,

Yue Liu

et al.

Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Recent groundbreaking preclinical clinical research underscores the pivotal role metabolite remodelling in pathology CVD. This metabolic transformation not only directly fuels progression CVD but also profoundly influences immune response within cardiovascular system. In this review, we focused on complex interactions between alterations responses during course Furthermore, explore potential therapeutic interventions that could be developed based understanding dysregulation By targeting these immunological pathways, novel strategies for prevention treatment CVDs might to improve patient outcomes reduce global burden disease.

Language: Английский

Fatty acid oxidation in immune function DOI Creative Commons

Felicia Kemp,

Erica Braverman, Craig A. Byersdorfer

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: June 27, 2024

Cellular metabolism is a crucial determinant of immune cell fate and function. Extensive studies have demonstrated that metabolic decisions influence activation, differentiation, cellular capacity, in the process impacting an organism’s ability to stave off infection or recover from injury. Conversely, dysregulation can contribute severity multiple disease conditions including autoimmunity, alloimmunity, cancer. Emerging data also demonstrate cues profiles success failure adoptive therapies. Importantly, immunometabolism not one size fits all; different types, even subdivisions within distinct populations utilize pathways optimize Metabolic preference change depending on microenvironment which cells are activated. For this reason, understanding requirements subsets critical therapeutically modulating states maximizing function for downstream applications. Fatty acid oxidation (FAO), particular, plays roles cells, providing both pro- anti-inflammatory effects. Herein, we review major available then focus more closely role FAO subsets. Understanding how why utilized by will allow design optimal therapeutic interventions targeting pathway.

Language: Английский

Citations

10
HBV and HBsAg strongly reshape the phenotype, function, and metabolism of DCs according to patients’ clinical stage DOI Creative Commons
Lucile Dumolard, Théophile Gerster, Florent Chuffart

et al.

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 29, 2025

Background: Hepatitis B is a liver infection caused by HBV. Infected individuals who fail to control the viral develop chronic hepatitis and are at risk of developing life-threatening diseases, such as cirrhosis or cancer. Dendritic cells (DCs) play important roles in immune response against HBV but functionally impaired patients with B. The underlying mechanisms involved HBV-induced DC dysfunctions remain be elucidated. Methods: We explored modulations HBsAg exposing blood-derived cDC1s, cDC2s, plasmacytoid DCs from healthy donors stimulating them toll-like receptor ligand. Their phenotypic functional features, well their metabolic profile, were analyzed through multiparametric flow cytometry multiplex assays further on patients’ samples. Results: found that deeply reshaped secretome Strikingly, we observed HBV-exposed secrete high levels CX3CL1 (fractalkine), chemokine responsible for attracting antiviral effectors site infection. exposure favored activation while drastically altering TRAIL expression ligand increasing secretion cytokines/chemokines tolerance. dampened metabolism subsets driving switches. Notably, relevance CX3CL1/CX3CR1 axis, TGF-β, disturbances was demonstrated within intrahepatic according disease stage. Conclusions: Our work brings new insights into immunomodulation induced DCs, which contribute responses progression toward chronicity.

Language: Английский

Citations

1
Age‐mediated gut microbiota dysbiosis promotes the loss of dendritic cells tolerance DOI Creative Commons
Hilal Bashir, Sanpreet Singh, R. P. Singh

et al.

Aging Cell, Journal Year: 2023, Volume and Issue: 22(6)

Published: May 9, 2023

Abstract The old age‐related loss of immune tolerance inflicts a person with wide range autoimmune and inflammatory diseases. Dendritic cells (DCs) are the sentinels system that maintain through cytokines regulatory T‐cells generation. Aging disturbs microbial composition gut, causing dysregulation. However, vis‐à‐vis role gut dysbiosis on DCs remains highly elusive. Consequently, we studied influence aging its impact DC tolerance. We show generated from either aged (DC Old ) or gut‐dysbiotic young Dysbiotic but not Young mice exhibited tolerance, as evidenced by their failure to optimally induce generation Tregs control overactivation CD4 + T cells. mechanism deciphered for was chiefly NF‐κB, impaired frequency Tregs, upregulation in level pro‐inflammatory molecules (IL‐6, IL‐1β, TNF‐α, IL‐12, IFN‐γ), decline anti‐inflammatory moieties (IL‐10, TGF‐β, IL‐4, IDO, arginase, NO, IRF‐4, IRF‐8, PDL1, BTLA4, ALDH2). Importantly, significant Lactobacillus genus noticed gut. Replenishing plantarum reinvigorated tolerogenic function rewiring metabolic pathways. Thus, first time, demonstrate This finding may open avenues therapeutic intervention treating age‐associated disorders .

Language: Английский

Citations

20
An early glycolysis burst in microglia regulates mitochondrial dysfunction in oligodendrocytes under neuroinflammation DOI Creative Commons

Hamid Suhail,

Mohammad Nematullah,

Faraz Rashid

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(10), P. 107921 - 107921

Published: Sept. 15, 2023

Metabolism and energy processes governing oligodendrocyte function during neuroinflammatory disease are of great interest. However, how varied cellular environments affect activity neuroinflammation is unknown. We demonstrate that activated microglial metabolism controls mitochondrial respiration activity. Lipopolysaccharide/interferon gamma promote glycolysis decrease myelin protein synthesis in rat brain glial cells. Enriched microglia showed an early burst glycolysis. In microglia-conditioned medium, oligodendrocytes did not respire expressed less myelin. SCENITH revealed metabolic derangement O4-positive endotoxemia experimental autoimmune encephalitogenic models. The was mediated by PDPK1 kinase B/AKT signaling. found microglia-produced NO itaconate, a tricarboxylic acid bifurcated metabolite, reduced oligodendrocytes. During inflammation, we discovered signaling pathway could be used as therapeutic target to restore induce remyelination.

Language: Английский

Citations

20
Metabolic adaptation to tyrosine kinase inhibition in leukemia stem cells DOI
Shaowei Qiu,

Vipul Sheth,

Chengcheng Yan

et al.

Blood, Journal Year: 2023, Volume and Issue: 142(6), P. 574 - 588

Published: May 16, 2023

Language: Английский

Citations

16
Polyunsaturated Fatty Acid–Bound α-Fetoprotein Promotes Immune Suppression by Altering Human Dendritic Cell Metabolism DOI Creative Commons
Paul V. Munson, Juraj Adamik, Felix J. Hartmann

et al.

Cancer Research, Journal Year: 2023, Volume and Issue: 83(9), P. 1543 - 1557

Published: Feb. 27, 2023

α-Fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell (DC) differentiation maturation block oxidative phosphorylation. To identify the critical metabolic pathways leading human DC functional suppression, here, we used two recently described single-cell profiling methods, scMEP (single-cell profiling) SCENITH energetic metabolism translation inhibition). Glycolytic capacity glucose dependence of DCs were significantly increased tumor-derived, but not normal cord blood-derived, AFP, uptake lactate secretion. Key molecules in electron transport chain particular regulated tumor-derived AFP. These changes occurred at mRNA protein levels, with negative impact on stimulatory capacity. Tumor-derived bound more polyunsaturated fatty acids (PUFA) than blood-derived PUFAs skewing promoted suppression. inhibited vitro, ω-6 conferred potent immunoregulation when Together, these findings provide mechanistic insights into how antagonizes innate immune response limit antitumor immunity.

Language: Английский

Citations

15
Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients DOI Creative Commons
Juraj Adamik, Paul V. Munson,

Deena M. Maurer

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 8, 2023

Abstract Efficacy of cancer vaccines remains low and mechanistic understanding antigen presenting cell function in may improve vaccine design outcomes. Here, we analyze the transcriptomic immune-metabolic profiles Dendritic Cells (DCs) from 35 subjects enrolled a trial DC late-stage melanoma (NCT01622933). Multiple platforms identify metabolism as an important biomarker patient overall survival (OS). We demonstrate multiple immune metabolic gene expression pathway alterations, functional decrease OCR/OXPHOS increase ECAR/glycolysis vaccines. To dissect molecular mechanisms, utilize single SCENITH profiling show clinical outcomes (OS) correlate with profile, that is linked to phenotype. With regulome profiling, MCT1 (monocarboxylate transporter-1), lactate transporter, increased DCs, glucose uptake secretion. Importantly, pre-vaccination circulating myeloid cells patients used precursors for generation are significantly skewed metabolically several subsets. Together, profile tightly associated immunostimulatory potential patients. link phenotypic changes signatures correspond suppressed differentiation.

Language: Английский

Citations

15
Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy DOI

Le Niu,

Miao Yu,

Zhiqin Cao

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3349 - 3361

Published: Jan. 17, 2024

Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective is spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate-

Language: Английский

Citations

4
Metabolic heterogeneity in tumor microenvironment – A novel landmark for immunotherapy DOI
Chen Chen, Peng Han, Yanping Qing

et al.

Autoimmunity Reviews, Journal Year: 2024, Volume and Issue: 23(6), P. 103579 - 103579

Published: June 1, 2024

Language: Английский

Citations

4
PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis DOI Creative Commons

Wenxiang Chu,

Weilin Peng, Yingying Lü

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(40)

Published: Aug. 9, 2024

Abstract Epigenetic regulation of metabolism profoundly influences cell fate commitment. During osteoclast differentiation, the activation RANK signaling is accompanied by metabolic reprogramming, but epigenetic mechanisms which induces this reprogramming remain elusive. By transcriptional sequence and ATAC analysis, study identifies that upregulates PRMT6 modification, triggering a switching from fatty acids oxidation toward glycolysis. Conversely, Prmt6 deficiency reverses shift, markedly reducing HIF‐1α‐mediated glycolysis enhancing acid oxidation. Consequently, or inhibitor impedes differentiation alleviates bone loss in ovariectomized (OVX) mice. At molecular level, reduces asymmetric dimethylation H3R2 at promoters genes including Ppard , Acox3 Cpt1a genomic accessibility for thus emerges as checkpoint, mediating switch to glycolysis, thereby supporting osteoclastogenesis. Unveiling PRMT6's critical role epigenetically orchestrating shifts osteoclastogenesis offers promising target anti‐resorptive therapy.

Language: Английский

Citations

4